Germicidal detergent compositions



United States Patent This application is a continuation-in-part of copending application Ser. No. 306,684, filed Sept. 5, 1963, and now abandoned; application Ser. No. 306,684 is a continuation-in-part of copending application Ser. No. 85,005,

filed Jan. 26, 1961, and now abandoned; and application Ser. No. 85,005 is a continuation-in-part of copending application Ser. No. 741,994, filed June 16, 1958, and now abandoned.

The present invention relates to germicidal detergent compositions, and more particularly to hydrophilic skin cleansing compositions comprising a skin substantive germicide. The compositions contemplated by this invention depend upon the presence of l-hydroxy-Z-pyridine thione, salts and esters thereof, and related compounds such as 2,2-dithio-pyridine-1-, l-dioxide as the substantive germicide.

It has become increasingly desirable to improve the bacteriostatic etfect of detergent compositions. The term detergent is intended to denote soap and nonsoap surface active agents. Many compounds are known that have germicidal or bacteriostatic properties against specific microorganisms or groups thereof, but such property is generally destroyed or seriously impaired when the compound is incorporated into detergent compositions.

The retention of germicidal properties by a compound after inclusion in a detergent composition is only one of 3,412,033 Patented Nov. 19, 1968 and retaining germicidal activity over a period of time after Washing and rinsing of the skin.

Other properties that are not concerned with the germicidal properties directly are, however, important as far as commercial use of the detergent composition by the general public is concerned. These include the following properties of a detergent bar, powder, liquid, etc., after inclusion of the specific compound:

(1) Initial whiteness.

(2) Color stability under sunlight exposure.

(3) Color stability under aging.

(4) Absence of discoloration by copper in stamping dies.

(5) Nonirritating to skin.

(6) No unpleasant odor.

It is an object of this invention to provide a detergent composition which exhibits substantive germicidal properties and has a prolonged effect in maintaining skin germs and bacteria at a reduced level.

It is another object of the present invention to provide a hydrophilic skin cleansing composition comprising a skin-substantive germicide.

It has been discovered that 1-hydroxy-2pyridinethione compounds when incorporated in detergent compositions retain their bacteriostatic properties and are skin substantive. The use of detergent compositions embodying 1-hydroxy-2-pyridinethione compounds retards the growth of body germs and bacteria for much longer periods than the use of detergent bases.

The specific procedures used to test the properties hereinbefore enumerated are described here in some detail, as there are no established procedures yet widely adopted in the art. The particular pyridinethione compound was blended at various concentrations with detergents which are anionic, cationic, nonionic, amphoteric and mixtures thereof, specific compositions thereof being set forth in Table I.

TABLE I Code Letter B C D E Luv 100 Ivory. 100 Dial". 100

Percent Detergent Compositions F G H I J K L M N O P Q Carney. 100 Cashmere Bouquet" Potassium Oleate "Ultrawet K (Anionic). Aerosol'OS" (Anionic) Aerosol'AY (Anionic). Carboxymethyl Cellulose "Tween 80 (Nonionic) Bn'j 35'." (Nom'onic) Pluronic F438 (Nonionic) Sterox AJi' (Nonionic)-- Parafiinj Intracol 0A" (Cationic) Antaron FC-34 (Amphoteric)- Mixed Phosphates- Key to Table I The first five soaps listed are well known proprietary soaps without germicidal agents, composed of a mixture of alkali metal salts of fatty acids, the general composition of Lux and Ivory being as follows:

Acids Lux Ivory (percent) (percent) Oleic and linoleic 45 46 S arlc 1D 14 Palmitic 30 30 Lower Fatty (myristic, lauric, etc.) 15 10 Potassium oleate is a liquid soap formed from 11 parts H20, 1 par KOH, 4 parts glycerin and 4 parts red 011 (oleic acid).

the necessary or desirable properties the compound must have to be considered as a desirable additive to the detergent composition designed for application to the human body. It is extremely important that the compound exhibit fgJ'ltrawet K is a sodium salt of sulfonated Gm petroleum hydrocar ons.

Aerosol OS is a sodium alkyl sulfonate.

Aerosol AY is diamyl sodium sulfosuccinate.

Tween 80 is a polyoxethylene sorbitan monooleate.

Brij 35 is a polyoxyethylene lauryl ether.

Pluronic F-GS is a condensate of ethylene oxide with a hydrocarbon base formed by condensing propylene oxide with propylene glycol.

Sterox AI is a polyoxyethyleue ether.

Intracol 0A is a long chain fatty acid amide containing several amine groups.

Antaron FC-34 is a complex fatty amide compound.

Bacteriostatic activity per se was tested -by taking plugs of the blended solid com-positions (liquid compositions were placed in peni-cups) and placing them on separate nutrient agar plates inoculated with Bacillus subtilis (found in soil and decomposing organic material), Staphsubstantivity, i.e., the property of remaining on the skin ylacoccus aureus (found on the human skin) and Sal- 3 4 monella typhosa (cause of typhoidfever). These three Substantivity was measured by soaking untanned calfbacteria are conventionally used in in vitro testing for acskin buttons in an 8% aqueous solution of the test soap, tivity and substantivity. The plates were incubated for 24 then repeatedly rinsing the buttons in distilled water, and hours at about 37 C. and then the diameter of the Zone subsequently placing the buttons on nutrient agar plates of no bacterial growth around each plug was measured 5 inoculated with the same bacteria as noted above. Therein millimeters (diameter of plug or peni-cup excluded) after, the procedure is the same as following for bacterioand recorded. static activity per se. The results are reported in Table II.

TABLE IL-BACTERIOSTAIIC ACTIVITY AND SUBSTANTIVITY Inhib. Zone-Diameter (mm.)

Number Additive Percent Soap Soap Plug Cal s S A T S A T 1 None (Control) B 0 0 O 0 0 2 do C 0 0 0 0 0 0 H 0 0 0 0 0 O I 20 14 20 0 0 0 J 30 26 24 0 6 0 K 0 0 0 0 0 0 L O 0 0 0 0 0 M 9 3 11 0 0 0 0. C 26 18 24 9 3 6 1 C 30 20 24 4 8 0. 5 B 33 22 28 9 5 6 1 B 35 22 28 9 8 8 0. 5 B 29 23 6 4 3 1 B 28 19 23 10 10 6 1 O 40 20 40 16 14 18 1 B 40 28 35 15 12 22 1 B 48 18 12 3 8 1 C 50 30 30 12 16 10 1 G 48 32 30 16 14 12 0. 5 G 46 31 30 9 13 10 0. 1 G 46 32 31 7 8 6 07 G 46 26 32 5 8 4 1 H 32 14 22 5 4 4 1 I 32 30 22 19 12 10 1 .l' 50 30 10 12 8 1 K 44 30 26 11 7 7 1 L 26 26 11 12 6 1 M 25 9 18 9 4 9 l B 40 13 24 14 4 12 07 B 30 18 22 6 6 4 07 C 31 21 21 6 7 5 0. 5 C 40 20 32 8 5 9 1 C 18 30 10 8 11 1 C 44 24 26 18 13 10 07 D 30 20 26 4 6 4 07 E 30 18 22 5 6 4 07 F 28 18 24 5 6 4 1. 0 G 48 46 16 16 12 0. 5 G 42 30 41 6 8 6 0. 1 G 34 28 34 4 6 4 07 G 32 27 30 4 3 3 1 H 38 16 24 14 7 7 1 I 30 28 20 10 11 8 1 J 40 30 40 8 8 6 1 K 42 18 22 10 9 5 1 L 32 26 28 8 6 4 1 M 20 8 16 2 2 1 1 B 50 18 25 15 9 16 0. 5 C 43 23 25 14 6 9 1 1 C 51 21 34 13 5 14 1. 0 G 46 34 40 16 16 12 0. 5 G 44 30 33 7 12 8 0. 1 G 42 28 30 5 7 5 07 G 38 27 30 6 7 3 1 C 42 22 28 18 10 10 1 H 24 14 18 1 0 Tr. 1 I 16 12 16 4 0 2 1 .1 28 18 20 2 1 2 1 K 27 14 36 4 1 8 1 L 34 10 19 4 2 5 1 M 22 17 15 5 2 1 1 B 30 14 20 14 3 12 l-H-2-P, manganous 1 C 40 28 28 9 10 8 1-H2P, zirconyl 1 C 45 34 31 15 15 10 1-H-2-P, lauryl pyridinium. 1 C 36 28 29 7 6 3 1-H-2-P, stannic.- 1 C 45 32 30 13 15 14 1-H-2-P, cadmium 1 O 22 21 19 11 9 9 1-H-2-P, manganous 0.75 C 46 30 28 14 15 12 0. 5 C 44 28 24 8 9 7 0. 1 C 34 25 22 T1. 0 0 0. C 43 28 32 12 12 9 0. 5 C 40 28 31 11 12 5 O. 1 C 30 23 22 Tr 0 0 0. 75 C 38 25 27 10 7 Tr. 0. 5 C 43 26 26 5 7 1 O. 1 C 32 26 21 Tr, Tr 0 0. 75 C 46 29 32 11 11 4 0. 5 C 40 29 31 15 14 11 0. 1 O 29 21 20 0 0 0 0. 75 C 25 21 16 10 10 10 0. 5 C 25 21 18 7 9 9 0. 1 C 24 20 15 2 6 2 1. 0 C 46 26 26 19 14 11 1. 0 C 42 22 26 13 14 11 1. 9 C 46 25 24 14 15 13. 5 1. 0 C 44 24 24 12 14 8 1. 0 C 41 23 24 7 10 5 1. 0 C 46 25 23 20 14 10 1. 0 C 26 19 18 Tr. 3 0 1. 0 C 46 26 26 19 15. 5 14 Key to Table II: S-Bac-illus s-ubtz'lis; ASzaphylocuccus aureus; T-Salmonella typhosa; 1H-2P1-hydroxy-2- ridinetiione- 1-H2P d1 11' "-dithiopyridine-1,l-dloxidc; Ziram-Zine dimethyldithiocarbamate; ThiramTetramethylthlurarn ausinna z an V It is clear from the results reported in Table H that the pyridinethione compounds exhibit both bacteriostatic activity and substantivity. Samples number 33 and 50 were further tested in a modification of the split-use hand washing test described by Quinn et al., Applied Microbiology 2, 2024 (1954). In the modified test, first the right hand was uncovered and the left hand covered with a neoprene glove. Then both hands were soaped for seconds by briskly rubbing the moistened medicated test bar with a small amount of wash Water held in the cupped hands, the lather being worked up as far as the wrists for 75 seconds, followed by rinsing the hands for 20 seconds while immersed in the wash water and then draining for 20 seconds. Thereafter, the left hand was uncovered, the right hand was covered with a neoprene glove, and the actual hand washing technique. Various other desirable properties of the same soap-pyridinethione compound mixtures of Table II are reported in Table IV.

The initial whiteness is reported both after mixing of the pyridinethione compound with the soap and after the soap bar had been formed in the conventional brass die.

The sunlight color stability was tested by breaking a soap bar in two and exposing one portion in an east window for two weeks, rotating it one-quarter turn daily.

The heat aging color stability was tested by placing a sample bar in a closed glass jar within an oven at 125 F. for two weeks, which is presumed to be approximately equivalent to one year shelf storage.

The tests reported in Table IV are of the same numbered samples of Table II, but all the samples of Table II were not tested here.

TABLE IV.COLOR CHANGES DUE TO AGING 1 See Table II.

2 This slight surface sheen, caused evidently by contact with the brass bar-forming die was removed before the oven and sunlight aging tests washing procedure repeated using unmedicated soap, i.e., control soap. Thus, the left hand serves as an unmedicated soap-washed control for the test soap-washed right hand.

The hands of each subject were washed three times each day and bacterial counts made on the wash water used in the second washing on the third and fifth days of the test. The control or unmedicated soap is used for the washings at which bacterial counts are made so that none of the test compound is present in the wash water to infiuence the results. Aliquots of the wash water in which each hand is washed were added to nutrient agar pour plates Within one minute after completion of washing. The plates were incubated for 48 hours at 37 C., the bacterial colonies counted and the results calculated for the entire wash water. The results are summarized in Table III:

It will be noted that samples 29 and 33 (zinc salt of I hydroxy 2 pyridinethione) gave excellent results in the color tests and, in fact, slightly better than the control bars containing no bacteriostatic agent. Samples 48 and 50 (2,2' dithiopyridine 1,1 dioxide) were also fairly good except for the surface sheen on the initial bar, a feature which might be overcome by changing the barforming conditions or dies.

The soaps showing the more desirable results in the color tests were subjected to bacteriostatic and substantivity tests after heat aging in an attempt to determine the extent of loss of bacteriostatic effect, if any, during heat aging. The B (Lux) soaps were aged for six weeks, a very severe test, while the C (Ivory) soaps were tested after the normal two Weeks aging at 125 F., as described for Table IV. Bacterio'static activity and TABLE II'LfiQPLIT-USE HAND WASHING TEST From the results reported in Table III, it will be noted that the bacteriostatic activity and substantivity of the substantivity were then determined by the same methods described and reported in Table II. Table V shows the pyridinethione compounds can be demonstrated in an post-aging results of these tests.

TABLE V.-BACTERIOSTATIC ACTIVITY AND SUBSTAN- TIVITY AFTER HEAT AGING Inhibition ZoneDiameter (mm) Weeks Number 1 Aged Soap Plug Calfskin Button 5 A '1 S A T 2 0 0 O 0 0 0 6 0 0 0 0 0 0 2 36 18 24 16 10 2 36 18 36 12 8 16 6 44 1o 16 1o 2 Tr. 20 6 33 12 20 13 7 13 2 42 13 22 10 7 14 2 44 12 11 7 ll 1 See Table II.

2 Tr.Growth touching button in one place.

After the aging tests, these samples retained their bacteriostatic activity and substantivity.

Detergent compositions N, O, P and Q were dry granular formulations of heavy-duty laundry type to which were added for separate test 1% by weight of zinc, so-

dium, disulfide and cetyl ammonium derivatives of the 1-hydroxy-2-pyridinethione. It was found that fabrics washed with these formulations had drastic reductions in bacteria count relative to fabrics washed in the same formulation without the active agent and further that this reduction was partly maintained after rinsing. Fabrics laundered in this manner would be particularly useful for wear or use that contacts the skin, or where large numbers of bacteria are encountered such as hospital or diaper laundries.

No skin irritation has been noted with any of the pyridinethione compounds tested.

The pyridinethione compounds do not impart odors to a detergent composition. This is a property highly desirable to both the manufacturer and the user of the detergent.

Not only do the pyridinethione compounds have excellent germicidal and substantive properties, which are maintained after prolonged aging, but these compounds also give excellent results in the various color tests which are so important in oifering soap to the consumer market. As will be noted, many of the compounds stay white through the heat aging and sunlight aging tests and the others have only slight discoloration.

The specific examples reported in the tables have included 0.07 to 5% by weight of the pyridinethione compounds in the detergent composition (based on solids) in order that specific comparisons could be made with the various compounds and also with various controls and.

prior art compounds. However, it will be obvious that a wider range of pyridinethione compounds can be used and we have found from 0.01 to 10% to be generally a satisfactory range, although this should not be a limiting feature of our invention.

It is obvious from these results that the l-hydroxy-Z- pyridinethione and its derivatives have properties which indicate their use as an ingredient of a germicidal or medicinal soap or detergent.

This invention is concerned with l-hydroxy-Z-pyridinethione (and derivatives) which has the following structural formula in tautomeric form, the sulfur being attached to No. 2 position of the pyridine ring:

N l 1%srr 5 3 Q-pyridinethiol-l-oxide, or 2-mercaptopyridine l-oxide 1-hydroxy-Z-pyridinethione specifically disclosed, it will be apparent to one skilled in the art that inorganic salts other than those tested are suitable. Further, other amine salts, quaternary ammonium salts and other esters are also suitable. The disulfide (2,2- dithiodipyridine l,1-dioxide) represents the attachment of two 1-hydroxy-2-pyridinethione rings by the elimination of the two hydrogens from the sulfur atoms to give a sulfur-to-sulfur linkage. Other substituted or derived compounds of l-hydroxy-2-pyridinethione which retain the bacteriostatic and substantive properties are considered to be within the scope of this invention.

The active pyridinethione compounds may be incorporated into liquid, bar or powder detergent compositions as desired to satisfy the particular product requirement. The detergent compositions herein are hydrophilic, but the composition as a whole may include hydrophobic components, e.g., paraffin. Detergent compositions may, of course, include conventional additives such as perfume, color, emollients, binders, inert fillers, etc.

What is claimed is:

1. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and a germicide selected from the group consisting of l-hydroxy-Z-pyridinethione, 2,2-dithiopyridine-l,l-dioxide, and inorganic metal salts of l-hydroxy-Z-pyridinethione in which the cation is selected from the group consisting of sodium, zinc, titanium, iron, manganese, zirconium, tin, cadmium, and barium, in an amount of from about .0l% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

2. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of an inorganic salt of l-hydroxy-Z- pyridinethione in which the cation is selected from the group consisting of sodium, zinc, titanium, iron, manganese, zirconium, tin, cadmium and barium, in an amount of from about .0l% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

3. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of the zinc salt of l-hydroxy-Z-pyridinethione in an amount of from about 01%; to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

4. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of the cadmium salt of l-hydroxy-Z-pyridinethione in an amount of from about .0l% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

5. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of the tin salt of 1-hydroxy-2-pyridinethione in an amount of from about .0l% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

6. A hydrophlic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic,

nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of the zirconium salt of l-hydroxy-Z-pyridinethione in an amount of from about .01% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said compositon.

7. A hydrophilic skin cleansing composition consisting essentially of at least one synthetic organic detergent selected from the group consisting of nonsoap anionic, nonionic, cationic and amphoteric detergents and fatty acid soaps and nonsoap surface active agents, and a germicide consisting of the titanium salt of I-hydroxy-Z-pyridinethione in an amount of from about 301% to about 10% by weight, said germicide being both skin-substantive and germicidally active in said composition.

References Cited UNITED STATES PATENTS 2,742,393 4/1956 Bernstein et a1. 167-33 2,742,476 4/1956 Bernstein et al 260294.8 2,809,971 10/ 1957 Bernstein et al 260270 2,846,398 8/1958 Beaver et a1 252-106 10 LEON D. ROSDOL, Primary Examiner.

S. E. DARDEN, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,412,033 November 19, 1968 Kenneth S. Karsten et al.

It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:

Column 8, lines 38, 50, 59 and 68, and column 9, lines 2 and 10, strike out "and nonsoap surface active agents", each OCCUTTBHCG Signed and sealed this 22nd day of July 1969.

(SEAL) Attest:

WILLIAM E. SCHUYLER, JR.

Edward M. Fletcher, Jr.

Commissioner of Patents Attesting Officer 

1. A HYDROPHILIC SKIN CLEANSING COMPOSITION CONSISTING ESSENTIALLY OF AT LEAST ONE SYNTHETIC ORGANIC DETERGENT SELECTED FROM THE GROUP CONSISTING OF NONSOAP ANIONIC, NONIONIC, CATIONIC AND AMPHOTERIC DETERGENTS AND FATTY ACID SOAPS AND A GERMICIDE SELECTED FROM THE GROUP CONSISTING OF 1-HYDROXY-2-PYRIDINETHIONE, 2,2''-DITHIOPYRIDINE -1,1-DIOXIDE, AND INORGANIC METAL SALTS OF 1-HYDROXY-2-PYRIDINETHIONE IN WHICH THE CATION IS SELECTED FROM THE GROUP CONSISTING OF SODIUM, ZINC, TITANIUM, IRON, MANGANESE, ZIRCONIUM, TIN, CADMIUM, AND BARIUM, IN AN AMOUNT OF FROM ABOUT .01% TO ABOUT 10% BY WEIGHT, SAID GERMICIDE BEING BOTH SKIN-SUBSTANTIVE AND GERMICIDALLY ACTIVE IN SAID COMPOSITION. 